Cytokines are a broad class of proteins that are secreted by various cell types, including cells of the immune system. One function of cytokines is to carry various signals between cells and thus control activity among cells. Several factors can cause cells to secrete cytokines, including a cell's encounter with pathogens that may cause disease. In certain instances, cells will secrete cytokines as a means of organizing a natural defense against the pathogen or disease.
There are numerous cytokines, such as interleukins (“IL”) produced by white blood cells. Individual interleukins include, for example, IL-2, IL-10, and IL-17A. Each of these interleukins have specific functions and effects, such as decreasing or increasing inflammation, stimulating the proliferation and function of various cell types, and regulating the production of antibodies. For example, IL-2 contributes toward inflammation and may be considered as inflammatory proteins, while IL-10 may be considered an anti-inflammatory protein that decreases inflammation. Therefore, the more IL-2 produced, the greater the inflammation and the more IL-10 produced the lesser the inflammation.
Interleukins have been determined to be involved in many processes, including, but not limited to, inflammation. For example, there is substantial evidence suggesting that IL-2 suppresses the production of immunoglobulins. In contrast, there is substantial evidence suggesting that IL-10 enhances immunoglobulin production.
Another cytokine is interferon-gamma or IFN-γ. IFN-γ is critical for innate and adaptive immunity against viral and intracellular bacterial defense functions and for tumor control. IFN-γ has been shown to alter the transcription of over thirty genes and to produce such affects as increasing T-helper (Th2) cell activity, promoting natural killer (NK) cell activity, and affecting various other molecular signaling pathways.
Other cytokines include tumor necrosis factor (TNF) alpha, or TNF-α, which is involved in the regulation of immune cells. Further, elevated production of TNF-α has been implicated as a contributing factor in a variety of human diseases, including cancer. TNF-α contributes to inflammation and may be considered an inflammatory protein. The more TNF-α produced, the greater the inflammation.
Yet another cytokine is granulocyte-macrophage colony-stimulating factor or GM-CSF. GM-CSF is a white blood cell growth factor that is known to stimulate stem cells, and is part of the immune/inflammatory cascade.
A transcription factor known as “nuclear factor kappa beta” or NF-κB is an intracellular protein that functions as a regulator of gene transcription and plays an important role in various biological processes and pathology. NF-κB has been found to play an important role in regulating the immune system in response to infection, and in several inflammatory pathways including the production of cyclooxygenase, nitric oxide synthase and other pro-inflammatory proteins. Inappropriate regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development and certain studies have linked NF-κB to processes involving synaptic plasticity and memory. The role of NF-κB and various cytokines is discussed in the article entitled Using Chemopreventive Agents to Enhance the Efficacy of Cancer Therapy, by Sarkar, et al., and published by the American Association for Cancer Research on Apr. 1, 2006, which is herein incorporated by reference in its entirety. Further, various viruses, including the HIV virus have molecular binding sites for NF-κB, thus indicating the NF-κB may be a critical component for activating the HIV virus from a latent state to an active state.
Therefore, the regulation of cytokines and/or transcription factors such as NF-κB can be a critical process in providing treatment for various ailments. For example, since IL-10 has anti-inflammatory properties, increasing IL-10 in a patient suffering from a chronic inflammatory condition can be used to treat the inflammation. Alternatively, since NF-κB is a factor for activating the HIV virus from a latent state to an active state, reducing the amount of NF-κB could delay or prevent the HIV virus from being activated.
Although there are known compositions and methods for regulating cytokines and NF-κB, many of these known compositions and methods are irritating to cells or have a toxic effect on cells. Further, many known compositions and methods for regulating cytokines and NF-κB regulate many cytokines in the same manner, some of which may hinder the overall desired effect of the treatment. For example, there are known compositions and methods for treating inflammation that up-regulate anti-inflammatory cytokines such as IL-10, but these compositions also result in up-regulation of IL-2, an inflammatory cytokine that reduces the effect of the IL-10.
Therefore, it would be advantageous to provide improved compounds, compositions and methods of regulating anti-inflammatory cytokines and transcription factors such as NF-κB on a cellular level. Moreover, providing compounds, compositions and methods that could regulate selected cytokines and transcription factors NF-κB to achieve a multitude of effects for the treatment of various health problems would be desirable. One example of such specific regulation of multiple cytokines would be selected compounds or a composition that up-regulates IL-10 without up-regulating IL-2, or even while down-regulating IL-2, thus increasing anti-inflammatory cytokines while reducing or maintaining the level of pro-inflammatory cytokines in order to reduce inflammation. It would also be desirable to provide selected compounds, compositions, and methods to affect various cytokines and transcription factors such as NF-κB that are not irritants, are non-toxic, easy to manufacture and distribute, and not expensive to produce, isolate and purify.